Insulin secretion is complicated process regulated by nutrients, such as glucose, free-fatty acids and amino acids, hormonal and neuronal factors which provides stimulatory and inhibitory influences on insulin secretion. Insulin release must be strongly controlled in response to change in blood glucose level. The disturbance of insulin secretion results in pathologic conditions such as diabetes mellitus, insulinoma and metabolic syndrome. Therefore, maintenance of insulin balance by regulation of insulin secretion is important and the regulation of insulin secretion is the key factor for improving different metabolic disorders.

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Regulation of Insulin secretion is mediated by metabolic pathways and extracellular signals acting predominantly via G-protein coupled receptors (GPCRs). Phospholipase Cβ (PLCβ) is one of the six isotypes (β, γ, δ, ε, ζ and η) and has principal role in GPCR-mediated signaling. The PLCβ family consists of four isozyme, PLCβ1 to β4, sharing their primary structure but each isozyme differs in regulatory properties. PLCβ hydrolyzes membrane-bound phosphatidylinositol 4,5-bisphosphate (PIP2) into inositol triphosphate (IP3) and diacylglycerol (DAG) which are an important second messenger in downstream signal pathway, regulating Ca2+ mobilization and PKC activation, respectively. The PLCβ is primarily activated by GTP-bound Gαq. In the pancreatic islet, there are GPCR which mediates stimulatory mechanism of insulin secretion such as M3 (Acetylcholine), CCK (CCKA), FFA (GPR40), and serotonin (HTR2b). However, the effect of PLCβ isozyme on regulation of insulin secretion is not fully understood in vitro and in vivo.

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In our lab, we created each PLCβ isozyme conditional knockout mouse to investigate the physiological role of PLCβ in pancreatic β-cells.